N,N-Diethylaniline → 4-[(4-Fluorophenyl)ethynyl]pyridine

Participants

Reaction Steps

4-pyridyl-hydroxymethyldiphenylphosphonate (6) (15.3 g, 46 mmol), diethylaniline (4 mL), and phosphorous oxychloride (50 mL) were warmed to 90° C. for 16 h. The reaction was quenched by pouring the reaction mixture over ice (400 g). Potassium carbonate was added until a pH of 8 was obtained for the solution followed by extraction with methylene chloride (3×200 mL). After drying ( MgSO4), the reaction was concentrated to afford crude 4-pyridyl-chloromethyldiphenylphosphonate (7) as a solid which was used in the next step without further purification: Mass Spectrum (CI) 360 (MH+). Potassium t-butoxide (3.30 g, 29.2 mmol) was added as a solid to 4-pyridyl-chloromethyldiphenylphosphonate (7) (5.00 g, 13.9 mmol), 4-fluorobenzaldehyde (8) (2.00 g, 15.3 mmol), and THF (70 mL) at 23° C. under argon. After 16 h, the reaction was quenched by adding to water (200 mL) over 3 min. After adjusting the pH of the solution to 7 with 1N HCl, the mixture was extracted with ethyl acetate (3×350 mL), and dried (MgSO4). After concentration in vacuo, the residue was purified by flash chromatography (ethyl acetate:methylene chloride 1:1) to afford 1-(4-pyridyl)-2-(4-fluorophenyl)ethyne (1) as a solid: Mass Spectrum (CI) 198 (MH+).

Provenance & Evidence